Synlett 2014; 25(20): 2842-2867
DOI: 10.1055/s-0034-1379166
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© Georg Thieme Verlag Stuttgart · New York

Enamide Derivatives: Versatile Building Blocks for Highly Functionalized α,β-Substituted Amines

Guillaume Bernadat
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France   Fax: +33(1)69077247   Email: Geraldine.Masson@cnrs.fr
,
Geraldine Masson*
Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles CNRS, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France   Fax: +33(1)69077247   Email: Geraldine.Masson@cnrs.fr
› Author Affiliations
Further Information

Publication History

Received: 25 July 2014

Accepted after revision: 28 August 2014

Publication Date:
06 November 2014 (online)


Abstract

As demonstrated by earlier successes with enamines, nitrogen-activated C=C double bonds have considerable potential for use in the construction of various nitrogen-containing products. To expand the applications of this class of substrates, we focused on studying the reactivity of enamides and enecarbamates as promising representatives. Starting from the well-known Povarov reaction, we gradually developed other cycloaddition reactions and, more generally, an extended range of methods for α,β-difunctionalization. Our most recent work, which involves radical processes, has contributed to a significant increase in the diversity of scaffolds accessible from these nitrogenous substrates and is potentially applicable to various natural and bioactive synthetic targets.

1 Introduction

2 General Design

3 Asymmetric Brønsted Acid-Catalyzed α,β-Difunctionalization of Enamides

3.1 Intramolecular α,β-Difunctionalization of Enamides Through Cycloaddition Reactions

3.1.1 Povarov Reactions

3.1.2 Diels–Alder Reactions of 1-Azadienes

3.2 Intermolecular α,β-Difunctionalization of Enamides

3.2.1 Mannich Reactions

3.2.2 Addition to Azo Compounds

3.2.3 Halogenation Reactions

4 Radical Tandem Difunctionalization: β-Alkylation Followed by α-Functionalization of Enamides

4.1 Photoredox-Mediated Tandem α,β-Difunctionalization of Enamides

4.1.1 Oxyalkylation

4.1.2 Oxy-, Amino- and Carbotrifluoromethylation

4.2 Single-Electron Transfer-Mediated Tandem α,β-Difunctionalization of Enamides

5 Conclusion

 
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